Natural products have been the single most productive source of leads for the development of drugs. Ninety five percent of the antibiotics described to date originate from leads discovered by screening natural product extracts or fractions. Many marketed antibacterial drugs are semisynthetic congeners of natural products, and are obtained from the chemical refinement of fermentation products (e.g., oritavancin, tigecyclin, telithromycin, rifampicin). Although a robust pipeline of natural-product based antibiotics recently existed, an unrelenting antimicrobial resistance to these medicines has eroded the physician's arsenal with which to treat infectious disease.
Over the past several decades, the frequency of antimicrobial resistance and its association with serious infectious diseases has increased at alarming rates. The increasing resistance to the current arsenal of antibiotics is of growing concern. A release by the National Institute of Allergy and Infectious Diseases (April 2006) reported that:                Nearly two million patients in the United States get an infection in the hospital each year. Of those patients, about 90,000 die each year as a result of their infection. This is up from 13,300 patient deaths in 1992.        In 2003, epidemiologists reported in the New England Journal of Medicine that 5 to 10 percent of patients admitted to hospitals acquire an infection during their stay, and that the risk for a hospital-acquired infection has risen steadily in recent decades.        More than 70 percent of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them.        Strains of S. aureus resistant to methicillin (MRSA) are endemic in hospitals and are increasing in non-hospital settings such as locker rooms.        A number of cases of community-associated MRSA have also been reported, including cases in patients without established risk factors.        The first S. aureus infections resistant to vancomycin (VRSA) emerged in the United States in 2002.        Increasing reliance on vancomycin has led to the emergence of vancomycin-resistant enterococci infections.        
Now that vancomycin resistance has been established in S. aureus, it is expected to increase at rates similar to those witnessed for vancomycin resistant enterococci, becoming endemic in United States hospitals by 2015. To maintain our current level of therapeutic efficacy, new antibiotics, with new mechanisms of action and chemotypes need to be developed.
The present invention is directed to overcoming these and other deficiencies in the prior art.